Serotonin1A receptors in the dorsal hippocampus regulate working memory and long-term habituation in the hemiparkinsonian rats

Ye Liu; Jian Liu; Si Rui Jiao; Xin Liu; Yuan Guo; Jin Zhang; Jie Yang; Wen Xie; Hui Sheng Wang; Li Zhang

doi:10.1016/j.bbr.2019.112207

Serotonin_1A receptors in the dorsal hippocampus regulate working memory and long-term habituation in the hemiparkinsonian rats

Behav Brain Res. 2019 Dec 30:376:112207. doi: 10.1016/j.bbr.2019.112207. Epub 2019 Aug 30.

Authors

Ye Liu¹, Jian Liu², Si Rui Jiao¹, Xin Liu³, Yuan Guo², Jin Zhang², Jie Yang², Wen Xie², Hui Sheng Wang², Li Zhang⁴

Affiliations

¹ Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an, 710061, China; Department of Clinical Medicine, School of Medicine, Xi'an Jiaotong University, Xi'an, 710061, China.
² Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an, 710061, China.
³ Department of Clinical Medicine, School of Medicine, Xi'an Jiaotong University, Xi'an, 710061, China.
⁴ Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an, 710061, China. Electronic address: zhangli1998@mail.xjtu.edu.cn.

PMID: 31476331
DOI: 10.1016/j.bbr.2019.112207

Abstract

Although the dorsal hippocampus (dHPC) and serotonin_1A (5-HT_1A) receptor are involved in cognition, their roles in cognitive impairments in Parkinson' disease (PD) are still unclear. In the present study, the effects of the 5-HT_1A receptor agonist 8-OH-DPAT and antagonist WAY100635 administrated into the dHPC of rats were assessed in T-maze rewarded alternation test for working memory and in hole-board test for long-term habituation. Unilateral 6-hydroxydopamine (6-OHDA) lesions of the medial forebrain bundle in rats impaired working memory and long-term habituation, decreased dopamine (DA) levels in the medial prefrontal cortex (mPFC), dHPC and ventral hippocampus (vHPC), and decreased the mean density of 5-HT_1A receptors and co-localization of 5-HT_1A receptor and excitatory amino acid carrier 1-immunoreactive (EAAC1-ir) neurons in the dHPC compared to sham-operated rats. Activation of dHPC 5-HT_1A receptors by local infusion of 8-OH-DPAT impaired working memory and long-term habituation in both sham-operated and the 6-OHDA-lesioned rats. Furthermore, blockade of dHPC 5-HT_1A receptors by WAY100635 improved the memories in the 6-OHDA-lesioned rats, but had no effects in sham-operated rats. Additionally, dHPC injection of 8-OH-DPAT decreased noradrenaline (NA) levels, increased 5-HT levels in the mPFC, dHPC and vHPC in sham-operated and lesioned rats, while WAY100635 increased DA and NA levels only in lesioned rats. The results of the present study suggest that dHPC 5-HT_1A receptors regulate cognitive impairments in PD by changes of monoamines in the related brain regions.

Keywords: 5-HT(1A)receptors; Dorsal hippocampus; Long-term habituation; Parkinson’s disease; Working memory.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

8-Hydroxy-2-(di-n-propylamino)tetralin / pharmacology
Animals
Disease Models, Animal
Dopamine / metabolism
Habituation, Psychophysiologic / physiology
Hippocampus / metabolism
Hippocampus / physiology
Male
Medial Forebrain Bundle / drug effects
Memory / physiology*
Memory, Short-Term / physiology
Neurons / metabolism
Parkinson Disease / metabolism*
Parkinson Disease / physiopathology
Parkinsonian Disorders / metabolism
Parkinsonian Disorders / physiopathology
Piperazines / pharmacology
Prefrontal Cortex / drug effects
Pyridines / pharmacology
Rats
Rats, Sprague-Dawley
Receptor, Serotonin, 5-HT1A / metabolism*
Receptor, Serotonin, 5-HT1A / physiology
Serotonin / metabolism
Serotonin Receptor Agonists / pharmacology
Temporal Lobe / metabolism

Substances

Piperazines
Pyridines
Serotonin Receptor Agonists
Receptor, Serotonin, 5-HT1A
Serotonin
N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide
8-Hydroxy-2-(di-n-propylamino)tetralin
Dopamine